A Practical Approach to the Use of Diabetes Medications

A Practical Approach to the Use of Diabetes Medications Juan Pablo Frias, M.D., FACE President, National Research Institute, Los Angles, CA Clinical Faculty, University of California, San Diego, CA

OUTLINE Pathophysiology of Type 2 Diabetes Natural history of Type 2 Diabetes Type 2 Diabetes Management Guidelines FDA-approved Therapeutic Options Case Studies

Pathophysiology of Type 2 Diabetes

Natural History of Type 2 Diabetes

Diabetes Drug Classes Increasing Rapidly

Type 2 Diabetes Therapy: Sites of Action

Key ADA Publications ADA = American Diabetes Association American Diabetes Association. Diabetes Care 2013:36(Suppl 1):S11-66. Inzucchi SE, et al. Diabetes Care 2012;35:1364-1379.

Managing Glucose in Type 2 Diabetes

General Glycemic Targets Measure ADA AACE A1C <7.0% 6.5% Preprandial capillary plasma glucose Postprandial capillary plasma glucose 70-130 mg/dl <110 mg/dl <180 mg/dl <140 mg/dl American Diabetes Association. Diabetes Care 2013:36(Suppl 1):S11-66. Garber AJ, et al. Endocrine Practice. 2013;19(Suppl 2):1-38.

Glycemic Targets Should be Individualized Inzucchi SE, et al. Diabetes Care 2012;35:1364-1379.

Metformin

Insulin Secretagogues

Secondary Failure Rate with SFU

Glitazones

Glucoregulatory Effects of GLP-1

GLP-1 is Rapidly Degraded by DPP-4

Strategies for Enhancing GLP-1 Action Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Inhibit the actions of DPP-4 FDA approved: sitagliptin, saxagliptin, linagliptin, alogliptin GLP-1 Receptor Agonists Resistant to DPP-4 inactivation Activators/agonists of the GLP-1 receptor FDA approved: exenatide, liraglutide, exenatide extended-release Drucker DJ, et al., Diabetes Care 2010;33(2):428-433

DPP-4 Inhibitors

GLP-1 Receptor Agonists

SGLT2 Inhibitors

Renal Handling of Glucose in a Non-Diabetic Individual

Renal Glucose Reabsorption is Increased in Type 2 Diabetes

Idealized Profiles of Human Insulin and Insulin Analogs

Insulin Delivery Devices

V-Go Disposable Insulin Delivery Devices

Complimentary Features of Basal Insulin and Incretin-based Therapy

CASE STUDIES

Case #1 58 year old obese Asian American male Type 2 diabetes diagnosed 5 years ago Taking metformin (2,000 mg/day); A1C=7.7% Family History: Type 2 diabetes and obesity (both parents) Notes: - Very fearful of injections and gaining weight - BMI 31kg/m 2

Case #1-Q1 How would you treat this patient to lower his A1C? A B C D E Add a SFU Add a TZD Start a SGLT-2 inhibitor Add a GLP-1 receptor agonist (exenatide or liraglutide) Add a DPP-4 inhibitor

Case #2 54 year old obese African American female Type 2 diabetes for 7 years On maximum dose of a SFU and DPP-4 inhibitor Long-standing difficult to control hypertension, mild CHF and mild renal insufficiency Labs - A1C: 7.6% (goal <7.0%) - LDL-C: 121 mg/dl - TG: 176 mg/dl - LFTs and TSH: Normal

Case #2-Q2 What medication(s) would be appropriate to initiate for at this time? A B C D Metformin TZD (pioglitazone or rosiglitazone) Bile acid sequestrant (colesevelam) SGLT-2 inhibitor (cana-, dapagliflozin)

Case #3 55 year-old Latino female Type 2 diabetes diagnosed 8 years ago PMH: HTN, dyslipidemia, sleep apnea and osteoporosis Social History: Housewife, has health insurance through husband s work, smokes ½ pack per day Complains of always being tired Medications: Metformin 1000 mg BID and glipizide 20 mg QD (regimen for 2 yrs) HCTZ 25 mg QD, lisinopril 20 mg QD, atorvastatin 20 mg QD

Case #3 Height 5 4 ; weight 198 lbs (BMI= 34 kg/m 2 ) BP=128/74 A1C=9.1% (goal <7.0%; 4 months ago 8.6%) Total cholesterol=194 mg/dl; LDL-C=120 mg/dl, HDL-C=42 mg/dl, TG=162 mg/dl Normal renal function

Case #3

Case #3-Q3 How would you treat Maria to lower her A1C? A B C D E F Add pioglitazone Nutrition and exercise counseling only Add a DPP-4 inhibitor Add basal insulin Add a SGLT2 inhibitor Add a GLP-1 receptor agonist

Case #3-Q4 What else would you consider during Maria s visit? A B Discuss medication adherence Check a TSH C. Counsel about smoking cessation D E F Consider aspirin therapy Consider increasing atorvastatin dose All of the above

Case #3 Insulin glargine initiated at 20 U every evening Metformin and glipizide continued at same doses Given instructions to titrate glargine by 2 U every 3 days until FPG in 100-120 mg/dl range TSH was normal and atorvastatin increased to 40 mg daily Initiated daily baby ASA and referred to smoking cessation counseling

Case #3 Returns to your office in 2.5 months Insulin glargine 58 U QHS No hypoglycemia A1C = 7.8%; Fasting glucose ~110 mg/dl Has gained 6 lbs

Case #3

Case #3-Q5 Maria s A1C is 7.8% and FPG is at goal. What would you do next to improve her glycemic control? A B C D E Add a DPP-4 inhibitor Increase glipizide dose Add a GLP-1 receptor agonist Add prandial insulin at breakfast Add a SGLT2 inhibitor

Case #3 Initiated liraglutide at 0.6 mg QD and increased over 4 weeks to 1.8 mg QD Mild nausea (no vomiting) during first 2 weeks which subsided Glipizide discontinued and insulin dose reduced by ~20% upon initiation of GLP-1 RA Clinical Pearl: With high post-dinner and bedtime glucose and near-normal fasting glucose, if basal insulin not reduced, improving post-dinner and bedtime glucose with GLP-1 RA could result in nocturnal hypoglycemia.

Case #3 A1C 1.1% (to 6.7%) and body weight ~8 lbs over the next 3-4 months A1C stable over a 9 month period on metformin 1000 mg BID, liraglutide 1.8 mg QD and insulin glargine 52 U QHS

KEY TAKEAWAYS Glycemic targets & glucose-lowering therapies should be individualized Diet, exercise and education are the foundations of therapy Unless contraindicated, metformin is optimal 1st-line drug After metformin, combination therapy with 1-2 other oral and/or injectable agents; minimize side effects Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glycemic control All treatment decisions should be made in conjunction with the patient (focus on preferences, needs and values) Comprehensive CV risk reduction is a major focus of therapy

Thank you very much! Juan P. Frias, MD jfrias@clinical-studies.com